Capitalizing on our experience in chromosome in situ hybridization, we have embarked on a new procedure designed to detect the expression of particular genes in tissue sections in situ. Using DNA or RNA probes, we have begun to analyze immunoglobulin, T cell receptor, and oncogene expression in cytocentrifuge preps of characterized cell lines, as well as in normal and malignant tissue specimens. The research and clinical utility of this technique would, we feel, be profound if it could be as easily and systematically applied as are current histochemical and immunocytochemical techniques. It allows for the detection of the expression of particular genes of interest within individual cells in tissue sections. It is of a very practical use in disease diagnosis as well as in an approach to basic questions of gene expression during development. We have demonstrated in a patient with CLL that this technique is complementary to and corroborative of the conventional molecular biological techniques of Southern and Northern blotting. We have expanded our analysis to the small cell lung cancer system where we are addressing the fundamental question of the relationship of expression of a member of the "myc" family of genes to tumor formation and tumor progression. We are now improving the sensitivity of this technique utilizing both radioisotopic and non radioisotopic (biotin) means of labelling our cRNA probes.